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In order to discover new bioactive compounds, the chemical constituents from the organic extracts of the cultured soft coral Klyxum simplex and wild-type soft coral Cladiella hirsute were studied. 27 new eunicellin-based diterpenoids, klysimplexins A¡VX (1¡V24) and klysimplexin sulfoxides A¡VC (25¡V27), were isolated from a cultured soft coral Klyxum simplex. Furthermore, eight new eunicellin-base diterpenoids, hirsutalins C (28) and F¡VL (29¡V35), were isolated from the soft coral Cladiella hirsuta. The structures of compounds 1¡V35 were elucidated by spectroscopic methods, in particular 1D and 2D NMR experiments. The absolute stereochemistries of 1, 3, 12, and 22 were determined by Mosher¡¦s method. The structure of 1 was further confirmed by a single-crystal X-ray diffraction analysis. The absolute configurations of 1, 3, 12, and 22 were determined by Mosher¡¦s method. Compounds 2, 8, 17, 20, and 29 have been shown to exhibit cytotoxicity toward a limited panel of cancer cell lines. Compounds 10¡V14, 18, 19, 25¡V28, and 31 were found to display significant in vitro anti-inflammatory activity in LPS-stimulated RAW264.7 macrophage cells by inhibiting the expression of the iNOS protein. Compounds 18, 19, and 27 also could effectively reduce the level of the COX-2 protein.

Taxol is a complex polyoxygenated diterpene isolated from Pacific yew (Taxus brevifolia). The structures of Taxoids are diversified with species, season and growth environment and the clinical effectiveness of Taxol as a microtubule-stabilizing therapeutic agent for treatment of several malignancies has motivated many scientists to isolate new taxoids and investigate their anti-tumor activities. In this continuing search for new and bioactive natural taxoids, reinvestigation of the acetone extract of the twigs, needles and branches of Taxus sumatrana (Taxaceae) afforded thirty-seven taxane diterpenes esters, including sumataxins sumataxin A (1)¡Bsumataxin B (2)¡Bsumataxin C (3)¡Bsumataxin D (4)¡Btaxuyunnanine C (5)¡B5a,7B,9a,10B,13a-petaacetoxy-4(20),11-taxadiene (6)¡B2a,5a,9a,10B,14B-pentaacetoxytaxa-4(20),11-taxadiene (7)¡B14B-hydroxytaxusin (8)¡B2a-deacetoxytaxinine J (9)¡Btaxa-4-(20),11-diene-2a,5a,7B,9a,10B,13a-hexaol hexaacetate (10)¡B1-dehydroxy baccatin VI (11)¡B7B,9a,10B,13a,20-pentaacetoxy-2a-benzoyloxy-4a,5a-dihydroxytax-11-ene (12)¡Btaxacin (13)¡Bbaccatin VI (14)¡Btaxuspinanane J (15)¡B2-deacetoxy-5-decinnamoyltaxinine J (16)¡BN-Methyl taxol C (17)¡B10-deacetyl yunnanaxane (18)¡Btaxumairol B (19)¡Btaxinine M (20)¡Bbaccatin III (21)¡Btaxuspinanane I (22)¡Btaxumairol K (23)¡Bwallifoliol (24)¡B13-oxo-baccatin III (25)¡Btaxol (26)¡B7-epi-10-deacetyl taxol (27)¡B10-deacetyl-13-oxo-baccatin III (28)¡B19-hydroxybaccatin III (29)¡B10-deacetyl taxol (30)¡B10-deacetyl-baccatin III (31)¡B13-acetyl-13-decinamoyltaxachinin B (32)¡B5-deacetyltaxachitriene B (33)¡B5-epicanadensene (34)¡Btaxezopidine F (35)¡B13a,7B-diacetoxy-2a,5a,10B-trihydroxy-9-keto-2(3¡÷20)abeotaxane (36)¡B2-deacetyl taxine B (37). The structures of new compounds were established on the basis of their spectroscopic analyses. Among them, compounds 1, 2, 3 and 4 are new compounds from natural source, 2a-deacetoxytaxinine J (9)¡Btaxuspinanane J (15) had effects on PBMC (Peripheral Blood Mononuclear Cells) proliferation, and sumataxin A¡BD (1¡B4) had light exhibitedactivity of HSV-1.

<p> The previously known, 8-oxo-(13→17)-pentanorlabda-12,19-dioic acid 19-methyl ester 36, was synthesised via two routes following the extensive investigation of the dehydrobromination of bromo-ketone 48, and also partial ozonolysis of the phenolic ring of podocarpic acid. </p> <p> This keto-acid 36 has been transformed to the corresponding 8-methylene compound in high yield. Application of the latter intermediate to diterpene synthesis has been demonstrated by the synthesis of 12-hydroxylabd-8(17)-en-19-oic acid 37 and methyl 12-ketolambertianate 61. </p> <p> During investigation of other synthetic intermediates a selective reducing agent for carboxylic esters in the presence of the carboxylic acid function - sodium trimethoxyborohydride, has been discovered. </p> / Thesis / Doctor of Philosophy (PhD)

Abstract In recent years, Taxus species have attracted a great interest because Paclitaxel, an anticancer agent, was isolated from T.brevifolia. Since the discovery of Paclitaxel many new taxane diterpenes from various Taxus species were isolated. In order to discover new taxoids, twigs and leaves of Taxus sumatrana (Miq.) de Laub. Growing in Taiwan were employed. Chromatographic separation of acetone extract of the leaves and twigs of the plant has yielded four taxane diterpenes and one derivative, designated tasumatrol M (1), tasumatrol N (2), tasumatrol O (3) and 7-deacetyl-canadensene (4). All structures were established primarily on the basis of 1D and 2D NMR techniques, including DEPT, COSY, HMBC and NOESY experiments. Compound 1, 2 and 3 were inactive as tested against human KB, Hepa59T, Hela, DLD-1 and WiDr tumor cell lines. Compounds 1 and 2, possessing a bicyclic skeleton, together with compounds 3 were new compounds from natural source. The possible biosynthetic pathway of compounds 1 and 2 were derived from geranylgeranyl pyrophosphate and verticillene.

This dissertation mainly discussed the investigation of five different soft corals collected in Green Island and one soft coral collected in Kenting. They were identified as Clavularia viridis, Xenia florida, Cespitularia taeniata, Cespitularia hypotentaculata, and Sarcophyton stolidotum. In the isolation of these corals, there were sixty natural products discovered, including twenty night new compounds and three new derivatives. The research of soft coral Clavularia viridis has result in the isolation of six new prostanoids, designated as 4-deacetoxyl-12-O-deacetylclavulone I (1), 4-deacetoxyl-12-O-deacetylclavulone II (2), bromovulone II (3), iodovulone II (4), 4-deacetoxyl-12-O-deacetylclavuloneIII (5), and bromovulone III (6), together with seven known prostanoids, identified as clavulone I (33), clavulone II (34), chlorovulone II (35), 4-deacetoxylclavulone II (36), clavulone III (37), chlorovulone III (38), and 7-acetoxy-7,8-dihydroiodovulone I (39). In the investigation of the soft coral Xenia florida, three new compounds called florxenilides A-C (7-9), has been purified. The research also obtained seven xenicane-type diterpenes, xeniafaraunol A (40), xeniafaraunol B (41), florlide A (42), florlide C (43), florlide D (44), 9-deoxyxeniolide A (45), and 9-deoxyxeniolide B (46) in addition to two cadinene-type sesquiterpenes, xenitorins A (47) and B (48). Florxenilides A and C also treated with some chemical reagents to afford three new derivatives, 10-benzoylflorxenilide A (10), Florxenilide C monoacetate (11), and 10-dehydroflorxenilide A (12). Otherwise, the study in Cespitularia taeniata has afforded ten new nitrogen-containing compounds, cespitulactams D-K (13-20) and taenialactams A-B (21-22), in addition to four known compounds, atractylenolactam (49), cespitulactam A (50), cespitulactam B (51), and cespitularin F (52). Moreover, there were three new compounds, namely cespihypotins E, F, and H (23, 24, 25) have been discovered from another soft coral Cespitularia hypotentaculata. The study of this coral also observed seven known components called cespihypotin G (53), cespitulactone A (54), cespitularin F (52), cespitularin D (56), cespihypotins A-C (55, 57, 58). Investigation of the non-polar extract of the soft coral Sarcophyton stolidotum collected in Kenting resulted in the isolation of seven new 14-membered carbocyclic cembranes, sarcostolides A-G (26-32), together with two known cembranes isosarcophytoxide (59) and isosarcophine (60). All the structures of above metabolites were elucidated by physical and spectroscopic analyses including IR, Mass, UV, NMR, and optical rotation, and by compared with published data in many previous papers. The stereochemistry of these compounds as determined by NOESY experiments, CD spectroscopic data, and Mosher¡¦s methods. Cytotoxicity tests were measured by Dr. Kuo Yao-Haur and Dr. Guh Jih-Hwa. Isolated marine prostanoids showed potent activities against human prostate carcinoma (PC-3) and colon adenocarcinoma (HT-29) cells. Among them bromovulone III (6) had the most potent cytotoxicity against both cell lines at IC50 0.5

As a part of search for bioactive natural products from the plants in collaboration with the Natural Products Discovery Institute (NPDI), ten plant extracts were investigated for their antiplasmodial activity against Plasmodium falciparum Dd2 strain. Twenty-eight compounds were isolated, and twelve of them were new compounds. The structures of all these compounds were determined by analysis of their mass spectrometric, 1D and 2D NMR, and ECD spectrum. Among these natural products, there were three compounds with good antiplasmodial activity, trichospirolide A with an IC50 value of 1.5 μM, malleastrumolide A with an IC50 value of 2.7 μM, and (+)-lariciresinol with an IC50 value of 3.7 μM. In addition to the studies of drug delivery of bioactive natural product, doxorubicin, a novel thiolated doxorubicin analog were designed and synthesized. Its analogs and PEG stabilizing ligands were then conjugated to gold nanoparticles and the resulting Au-Dox constructs were evaluated by TEM. The release of native drug can be achieved by the action of reducing agents, and that reductive drug release gave the cleanest drug release. / Ph. D.

No / Croton membranaceus is used by herbalists and traditional healers in Ghana for the management of various cancers, especially prostate cancers. A methanolic extract of the roots showed cytotoxic activities against two cancer cell lines, and bioassay-guided fractionation of this extract revealed that the cytotoxic activity resided mostly in the ethyl acetate fraction. Six compounds were isolated from this fraction, including a new furano-clerodane diterpenoid (1), for which the trivial name crotomembranafuran is suggested. This compound exhibited an IC50 value of 4.1 microgram/mL (10.6 microM) against human prostate (PC-3) cells, providing some support for the traditional use of C. membranaceus in the treatment of cancers

Soft corals of the genus Briareum (Briareidae) have been well known as a rich source for marine natural products with novel structural features. Briarane-related natural products attracted the attentions of researchers because of the structural complexity and interesting biological activity associated with numerous compounds of this type. Previous studies on the secondary metabolites of wild-type and cultured Formosan octocoral Briareum excavatum were collected around the sea area of Kenting. In the thesis of our studies on secondary metabolites from marine organisms, the acetone-soluble of the Formosan octocoral B. excavatum collected at Orchid Island has led to the isolation of eleven briarane-type diterpenoids (1−11), compounds 3, 4, and 6−10 are new compounds. The structures of these compounds were determined on the basis of their spectroscopic analysis (1H NMR, 13C NMR, 1H−1H COSY, HSQC, HMBC, NOESY, IR and mass spectra) and physical data by comparison of the physical and spectral data with those of the related literatures. The antiviral activity against HCMV (human cytomegalovirus) cells of these secondary metabolites was evaluated. Metabolite 8 exhibited significant activity against HCMV cells and compound 11 showed anti-inflammatory activity.−